ArticlePharmacology research & perspectives2015
Evaluation of biomarkers for in vitro prediction of drug-induced nephrotoxicity: comparison of HK-2, immortalized human proximal tubule epithelial, and primary cultures of human proximal tubular cells.
Article in Pharmacology research & perspectives, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Perturbation of metabolic pathways associated with exposure of human renal proximal tubular cells to nephrotoxic pollutants and drugs.Toxicology · 2026Article
- Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Hyperoside mitigates amphotericin B-induced nephrotoxicity in HK-2 cells via bioenergetic and oxidative stress modulation.BMC pharmacology & toxicology · 2025Article
- Comparative Analysis of Proximal Tubule Cell Sources for In Vitro Studies of Renal Proximal Tubule Toxicity.Biomedicines · 2025Article
- Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.Scientific reports · 2025Article
- Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage.Clinical and translational science · 2023Article
- Article
- Functional Evaluation and Nephrotoxicity Assessment of Human Renal Proximal Tubule Cells on a Chip.Biosensors · 2022Article
- Human iPSC-derived renal organoids engineered to report oxidative stress can predict drug-induced toxicity.iScience · 2022Article
- Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients.International journal of molecular sciences · 2021Article
- The effect of repeated passaging on the susceptibility of human proximal tubular HK-2 cells to toxic compounds.Physiological research · 2020Article
- Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells.Nanomaterials (Basel, Switzerland) · 2020Article
- The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity.International journal of molecular sciences · 2019Review
- Cell-free hemoglobin augments acute kidney injury during experimental sepsis.American journal of physiology. Renal physiology · 2019Article
- BPEI-Induced Delocalization of PBP4 Potentiates β-Lactams against MRSA.Biochemistry · 2019Article
- Bromate-induced Changes in p21 DNA Methylation and Histone Acetylation in Renal Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Structure-Function Studies of Polymyxin B Lipononapeptides.Molecules (Basel, Switzerland) · 2019Article
- A Fluorescent Glucose Transport Assay for Screening SGLT2 Inhibitors in Endogenous SGLT2-Expressing HK-2 Cells.Natural products and bioprospecting · 2019Article
- A human proximal tubule-on-a-chip to study renal disease and toxicity.Biomicrofluidics · 2019Article
- Emerging Kidney Models to Investigate Metabolism, Transport, and Toxicity of Drugs and Xenobiotics.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
There has been intensive effort to identify in vivo biomarkers that can be used to monitor drug-induced kidney damage and identify injury before significant impairment occurs. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and human macrophage colony stimulating factor (M-CSF) have been validated as urinary and plasma clinical biomarkers predictive of acute and chronic kidney injury and disease. Similar validation of a high throughput in vitro assay predictive of nephrotoxicity could potentially be implemented early in drug discovery lead optimization to reduce attrition at later stages of drug development. To assess these known in vivo biomarkers for their potential for in vitro screening of drug-induced nephrotoxicity, we selected a panel of nephrotoxic agents and examined their effects on the overexpression of nephrotoxicity biomarkers in immortalized (HK-2) and primary (commercially available and freshly in-house produced) human renal proximal tubule epithelial cells. Traditional cytotoxicity was contrasted with expression levels of KIM-1, NGAL, and M-CSF assessed using ELISA and real-time quantitative reverse transcription PCR. Traditional cytotoxicity assays and biomarker assays using HK-2 cells were both unsuitable for prediction of nephrotoxicity. However, increases in protein levels of KIM-1 and NGAL in primary cells were well correlated with dose levels of known nephrotoxic compounds, with limited correlation seen in M-CSF protein and mRNA levels. These results suggest that profiling compounds against primary cells with monitoring of biomarker protein levels may have potential as in vitro predictive assays of drug-induced nephrotoxicity.
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